A burden of lingering senescent cells contributes to the chronic inflammation of aging and is disruptive to tissue structure and function. Excess visceral fat tissue is know to generate an increased burden of senescent cells. It does also dysregulate metabolism and provoke chronic inflammation in a range of other ways, however. So while senescent cells appear to be important in the damage done by obesity, it remains unclear as to what degree the use of senolytic drugs to selectively destroy senescent cells will reduce the consequences of obesity. Answers will emerge in time, but, as ever, making progress towards larger clinical trials and sufficient human data is a slow and expensive process. There is little incentive for industry to fund work on the existing cheap, off-patent senolytics, such as the dasatinib and quercetin combination, and the usual alternative path of developing and testing expensive, new, patented drugs takes as long as it takes.
Obesity and type 2 diabetes mellitus (T2DM) represent currently major health threats worldwide owing to their rapidly increasing prevalence and debilitating long-term chronic complications. Senescent cells play an important role in T2DM pathogenesis via direct impact on pancreatic β-cell function, since reduced pancreatic β-cell mass and subsequent defects in insulin secretion are major factors in the pathogenesis and progression of T2DM. Preferential accumulation of senescent cells in visceral adipose tissue (VAT) is then associated with an inappropriate expansion of adipocytes (hypertrophy), insulin resistance, and dyslipidemia and represents the nexus of mechanisms involved in aging and age-related metabolic dysfunctions. On the other hand, changes induced by long-standing, poorly controlled T2DM are linked to the accumulation of premature senescent cells in various tissues, contributing to the development of chronic irreversible complications. Thus, senescence is both a cause and a consequence of obesity and T2DM.
The presence of T2DM and its complications is the major reason for the massive financial burden of the treatment of T2DM. It is estimated that therapy of diabetic complications consumes up to two-thirds of the overall T2DM treatment costs. Despite the availability of novel glucose-lowering drugs, the number of patients with T2DM and related chronic complications keeps increasing at a high rate. Current pharmacological approaches address the pathophysiological defects present in T2DM rather than preventing the processes contributing to its development. Therapeutic targeting and elimination of senescent cells with suppression of the SASP production by senolytics may therefore be an effective strategy for a novel approach in the treatment of metabolic diseases.
Link: https://doi.org/10.3...ll.2025.1622107
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